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Bioc 406 > Fatty Acid Synthesis > Flashcards

Fatty Acid Synthesis Flashcards

1
Q

Where does fatty acid synthesis occur?

A

The cytoplasm

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2
Q

What molecule is the building block for fatty acid synthesis?

A

Acetyl-CoA

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3
Q

Acetyl-CoA is created in the matrix, but fatty acid synthesis occurs in the cytoplasm. How does acetyl-CoA reach the cytoplasm?

A

Via the citrate shuttle

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4
Q

What are the reactants + products of the citrate shuttle?

A

1 NADH, 2 ATPs are used

1 NADPH is generated

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5
Q

What are benefits of the citrate shuttle? (3)

A
  1. NADPH will be used later on during fatty acid synthesis
  2. The movement of Acetyl-CoA from the matrix to cytosol is independent of Acetyl-CoA concentration
  3. Conezyme A is preserved inside the mitochondria (if we had an Acetyl-CoA shuttle, it would be deprived of and this would negatively affect biochemical processes)
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6
Q

What is the function of Acetyl-CoA carboxylase?

A

It adds a CO2 group to Acetyl-CoA to form Malonyl-CoA

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7
Q

What is the first committed step in fatty acid synthesis?

A

When ACC is utilized

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8
Q

True or False: The synthesis of Malonyl-CoA through use of ACC is highly exergonic and is essentially irreversible.

A

True

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9
Q

True or False: Through the use of ATP, HCO3- is added onto biotin in the “biotin carboxylase” domain.

A

True

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10
Q

True or False: Biotin is carried on the “biotin carboxylase” domain.

A

False - Biotin is carried on the “biotin carrier protein” domain

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11
Q

True or False: All 3 domains of ACC are found on separate polypeptide chains.

A

False - All 3 domains of ACC are part of a SINGLE polypeptide chain (Human ACC)

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12
Q

Now that the “biotin carrier protein” domain has CO2 attached to biotin, it swings to the right and bring the reactive CO2 to the ____ ____ where ____ is located.

A

Active site, Acetyl-CoA

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13
Q

What is the structure of ACC? [Specifically list its size, and the domains it contains.]

A
  • 500kDa dimer

- Contains a biotin carboxylase domain, a biotin carrier protein domain, and a carboxyl-transferase domain

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14
Q

How many active sites are present in ACC?

A

2 active sites

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15
Q

The reactive CO2 must swing from one active site to another. How much does the BCCP domain have to be rotated?

A

180 degrees

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16
Q

How many enzymes are required for fatty acid synthase?

A

6 enzymes

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17
Q

What is the function of the enzyme Thioesterase?

A

It releases the fatty acid chain from the Fatty Acid Synthase complex
(note - it only engages when the fatty acyl chain reaches 16 C in length!)

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18
Q

What is ACP? What is it attached to?

A
  • Stands for acyl carrier protein
  • ACP is covalently attached to a pantothenate cofactor has a reactive SH (thioester) group that carries the growing fatty-acyl group
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19
Q

True or False: In E. Coli, the 6 enzymes are all on separate proteins, while in humans, all enzymes are on a single polypeptide chain.

A

True! During evolution, all the enzymes combined into a single protein.

20
Q

True or False: The KS domain has a catalytic cysteine residue (SH).

A

True

21
Q

True or False: The ACP domain is linked to the Ketoacyl-Reductase (KR) domain by a long flexible polypeptide segment.

A

True

22
Q

What is step 1 of the FAS reaction?

A

Transacylation: the acetyl group from Acetyl-CoA is added onto the SH group of ACP, then transferred onto the SH group of KS. This opens up space for SH on ACP to accept Malonyl-CoA

23
Q

What is step 2 of the FAS reaction?

A

Condensation - CO2 from Malonyl-CoA is removed from ACP and it combines with Acetyl-CoA on the SH of the KS domain

24
Q

What is significant about step 2 of the FAS reaction?

A

The release of CO2 drives the reaction forward and makes it irreversible

25
Q

What is step 3 of the FAS reaction?

A

Reduction (Keto reductase) - NADPH (the one made from the citrate shuttle) is used to reduce C=O to CH-OH

26
Q

What is step 4 of the FAS reaction?

A

Dehydration - this forms a double bond CH=CH

27
Q

What is step 5 of the FAS reaction?

A

Reduction - NADPH is used to reduce CH=CH to CH2-CH2

28
Q

What is the architecture of fatty acid synthase?

A

-534 kD dimer

29
Q

What is the primary product of fatty acid synthase?

A

Palmitate

30
Q

Where does elongation of fatty acids occur?

A

Mostly in the ER, some in the mitochondria

31
Q

True or False: For synthesis of longer fatty acid chains, separate enzymes are used, instead of a single complex.

A

True

32
Q

True or False: For synthesis of longer fatty acid chains, fatty acyl-CoA and malonyl-CoA are used instead of malonyl-ACP.

A

True

33
Q

What is the function of desaturases?

A

They form cis-double bonds

34
Q

How many desaturases do humans have and what are they?

A

4 desaturases

Delta 4, Delta 5, Delta 6, and Delta 9

35
Q

Where are desaturases located?

A

ER membrane

36
Q

What additional desaturases do plants have?

A

Delta 12 and Delta 15

37
Q

True or False: Essential fatty acids like Omega-6 are needed as precursors for the synthesis of fatty acids such as Arachidonate.

A

True

38
Q

Where is Arachidonate stored and what triggers its release?

A
  • It is stored in membranes as a phosphoglyceride

- It is released by Phospholipase A2

39
Q

List 3 signaling molecules that fall under Eicosanoids (potent hormones).

A
  1. Prostaglandins
  2. Thromoxanes
  3. Leukotrienes
40
Q

What is the function of prostaglandins?

A
  • Elevate fever
  • High levels lead to pain and inflammation
  • Stimulate smooth muscle contraction
  • Impact blood flow
41
Q

What is the function of thromoxanes?

A
  • Formation of blood clots

- Reduce blood flow at blood clot sites

42
Q

What is the function of leukotrienes?

A

-They are signaling molecules in the immune response

43
Q

What do NSAID drugs like aspirin and advil drugs do?

A

They block PGH2 synthase, thus they block the conversion of arachidonate to PGH2 (which is involved in pain and inflammation)

44
Q

What’s another word for PGH2 synthase?

A

COX

45
Q

Molecularly, what is aspirin doing?

A

Aspirin blocks the channel in PGH2 synthase which arachidonate enters through to access PGH2’s catalytic site

Bioc 406 (15 decks)

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